There is presently a need for methods of treatment for drug abuse involving such drugs as amphetamine and amphetamine-related drugs exhibiting similar pharmacological effects as amphetamine.
Amphetamines in large doses cause psychotomimetic effects that resemble acute paranoid schizophrenia and are relieved by neuroleptics, which are the primary antipsychotic drugs used in the treatment of schizophrenia (Snyder and Largent (1989) J. Neuropsychiatry 1: 7-15). The neuroleptics cinuperone (HR375), chlorpromazine, haloperidol, and clozapine have been reported to antagonize the effects of amphetamine in animals (Hock et al. (1985) Drug Development Research 6: 301-311). Some neuroleptics, such as tiospirone, haloperidol, and cinuperone, exhibit high affinity and non-selective binding to both sigma receptors and dopamine D.sub.2 receptors (Snyder and Largent (1989) J. Neuropsychiatry 1: 7-15). Since the behavioral effects of amphetamines derive primarily from the synaptic release of dopamine, it is believed that the antagonism of the effects of amphetamine by neuroleptics is mediated by antagonism of the dopamine receptor system by neuroleptics.
The antipsychotic BMY14802, which exhibits relatively selective binding to sigma receptors relative to dopamine D.sub.2 receptors, has been reported to antagonize amphetamine-induced behavioral changes considered to be relevant to psychosis (Schlemmer and Davis (1986) Soc. Neurosci. Abstr. 12: 480).